equilibrium and kinetic studies of monoaquo complexes of platinum(i1). 2. dimerization of pt (dien)...

8/9/2019 Equilibrium and Kinetic Studies of Monoaquo Complexes of Platinum(I1). 2. Dimerization of Pt (dien) ( HzO)2'

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Inorg.

Chem. 1987, 26,997-999 997

undergoes hydrolysis. Both the somewhat greater tran s effect of

chloride (vs. ammo nia) an d the 2 /1 statistical factor favor hy-

drolysis for this complex compar ed to the am ino acid complexes.

Finally, the extent of hydrolysis of these amino acid complexes

(as measured by

Kh)

s substantially less than tha t of Pt(en)C12.z1

This can be attributed to a sub stantial negative cis influence of

the dimethyl sulfoxide, augmente d by the 2/ 1 statistical factor

for Pt(en)C12.

Mechanism

of

Hydrolysis by OH-.

The contrasting behavior

of the th ree amino acid complexes in their reaction with hydroxide

ion

can be

accounted for on the basis of their structura l differences.

Both glycine and sarcosine complexes contain an N H proton. The

pK, of such protons has been estimated to be about 15. Thus,

addition of OH - sufficient to produce a pH of 10-12 would

produce a significant concentration of the conjugate base of these

complexes by

loss

of the N H proton. The importance of this

conjugate base mechanism for substitution reactions has long

been

recognized>2 but it is not clear why the chelate ring a nd not th e

chloride of the conju gate base is

so

readily a ttacked by OH-. The

large trans effect of Me zSO is probably an imp ortant factor.

Loss

of the N H proton should greatly strengthen the R-N bond in the

same way that

loss

of a proton from coordinated water strengthens

the

Pt-0

bond. This might

be

expected to lead to loss of the

C1-

t rans to N but the ring-opening reaction is also facilitated: the

Barton,

J

K.; Lippard, S.

. Ann. N.Y. cad. Sci.

1978, 313,686.

The

argument

here

is

similar to

the

explanation

of

the

effect

of

sub-

stitution

of N H

protons on the kinetics

of

base hydrolysis

of Pd-

(dien)CI+:

Bradley, W . H.;

Basolo, F.

.

Am . Chem. Soc.

1964, 86,

2075; 1966,88, 2944.

ring-opening reaction prevails. For the N,N-dim ethylglycin e

complex, by con trast, the ring-opening reaction does not occur

to a significant extent in competition with t he hydrolysis reaction.

This unexpected ring-opening reaction by OH- is comparable

to the unexpected c is(N ,N) addition of a second mole of amino

acid to th e aqu o species derived from the preferred isomer of

Pt(alanine)(Me2S O)C1, which Kukushk in and Garganov a first

r e ~ 0 r t e d . l ~his reaction led them to the wrong conclusion about

the stereochemistry of the compound, which they incorrectly

identified as the tran s(N,S ) isomer. At high p H values, other

ligands will readily displace the

0

of the coordinated carboxyl

group. For the reaction with

OH-,

the effect is strictly a kinetic

effect. Given enough time, the predo minant species is the ring-

closed, chloride-substituted species that would result from simple

displacement.

An un derstanding of the chemistry of the formation of aqu o

(and hydroxo) species from chloro species has enabled

us

to

prepare aqu o species readily and to analyze the acid-base and

dimerization properties of these aquo species and of Pt(dien)-

Th e report of such investigations of these am ino acid-

Mez SO complexes will include analysis of the relative importance

of chloro, aquo, hydroxo, and dimer species as a function of p H

and pCl.23

Acknowledgment

is made to the donors of the Petroleum R e-

search Fund, administered by the Amer ican Ch emical Society,

for support of this research.

(23)

Erickson, L. E.; Burgeson, I. E.; Eidsmoe,

E.;

Larsen, R. G., in

prepa-

ration.

Contribution from the Department of Chemistry,

Grinnell College, Grinnell, Iowa 501

12

Equilibrium and Kinetic Studies of Monoaquo Complexes of Platinum(I1). 2.

Dimerization of P t dien) HzO)2

Luther

E. Erickson,*

Hans L.

Erickson,

and

Tara

Y Meyer

Received September IO, 986

The dimerization of Pt(d ien)( OH Jz+ by reaction with the conjugate base Pt(dien)(OH)+

o

form the p-OH-bridged species has

been investigated by pH methods. Rate constants at

35 OC

for both dimerization

(kd

=

3.3

X

M-

s-l) and dissociation

kd

=

3.0

X

s-l

and the equilibrium constant

Kd

108M-I)

for the reaction were obtained

by

monitoring the pH after partial

titration with Na OH . The significance of these

data

is illustrated

with

species distributio n curves of dimer as

a

function

of

pH

and total platinum concentration.

The a queou s solution chemistry of platin um complexes has

attracted considerable interest in the last few years, owing in part

to its pertinence to use of cis-platinum an d related compoun ds

in cancer chemotherapy. ' Among the most studied platinum

chelates are th e diethylenetriamine complexes, which have t he

advan tage of relatively simple chemistry for substitutio n reactions.

Th e chloro complex [Pt(dien)C l]Cl h as been used extensively to

probe the details of the reaction of D N A nucleotides and

nu-

cleosides with a labi le plat inum s p e c k z Mart in and co-workers

have employed th e analogous palladium

species,

which had parallel

chemistry but which reac ts more rapidly. ,

In

spite of the fact that Pt(dien)Cl+ has been studied extensively

for many years, confusion about the m echanism of its substitution

reactions is still evident. Beattie4 has recently provided an al-

ternative interpretation of kinetic data for anatio n of Pt(dien )-

(OH2)+ , 5which had been cited as evidence for a 3-coordinate

intermed iate in the reaction.6 His interpretation provides values

for the r ate constants for th e hydrolysis reaction

ki

Pt(dien)Cl+ H 2 0 t (di e11 )(0H ~)~ + C1-

1 )

and for the corresponding equilibrium constant

K h

= k , / k 2 .

In

their study of the aqueous solution chemistry of Pd-

(dien)(OH2)2+,Mar tin and L im obtained evidence for the for-

mation

of

a

p-OH

bridged dimer of the aquo species.' The

reaction can be formulated

P d(d ie11) (0H~)~+ P d(d iene ) (OH)+

-

( d i e ~ ~ ) P t - O H - P t ( d i e n ) ~ +

Hz O

( 2 )

For reaction 2 a t 25

OC

and 0.5

M

KNO,, Scheller and Martin

obtained a n equilibrium constant, Kd, of 132 M-I.* However,

as Martin has pointed out in reviewing the hydrolytic equilibria

(1)

Lippard,

S. . Science Washington, D.C.)

1982, 218, 1075.

(2)

Kong,

P.

C.; Theophanides, T. Inorg. Chem.

1974, 13, 1981.

(3)

Martin, R.B.

In

Platinum, Gold, and Other Metal Chemotherapeutic

Agents; ACS Symposium Series

209;

American

Chemical Society:

Washington DC,

1983;

p

231.

(4) Beattie,

J. K norg. Chim . Acra

1983, 76, L69.

5 ) Gray,

H.

B.;

Olcott,

R. J. Inorg. Chem.

1962,

I

481.

(6)

Mureinik, R. J. Coord. Chem. Rev.

1978, 25,

1.

(7) Lim,

M. C.;

Martin,

R. B.

J .

Inorg. Nucl . Chem.

1976, 38, 1911.

(8)

Scheller, K.; Sheller-Krattiger V.;

Martin,

R. B. J . Am. Chem. SOC.

1981, 103, 6833.

0020-1669/87/1326-0997 01.50/0 1987 American Chem ical Society



998 Inorganic Chemistry, Vol

26,

No 7, 1987

in these systems, the corresponding dimerization reaction in

P t (d i en ) (O H 2 ) z+ a w a it s ~ t u d y . ~

s

part of a broader study of the aqueous solution chemistry

of mon oaquo platinum species, we have recently obtained both

rate an d equilibrium data for the dimerization of these platinum

species, Le., for the process that we will abbreviate

Er ickson e t a l .

P t-OH22+

Pt-OH+

Pt-OH-Pt3+ H20

(3)

k

The data are of interest in themselves, and the pH relaxation

method employed

to

follow the reactions is probably generally

applicable to similar systems. For any partially neutralized

so-

lution of the acidic aquo species, the effect of the dimerization

is to change the ratio of acid to conjugate base, and hence to

change the pH. If less than half of the acid is neutralized, the

pH will drop a s dimerization occurs; if more tha n half, it will

increase. For a half-neutralized solution, the pH will rema in

constant a s dimerization occurs.

In

practice, about 10%

or

90

neutralization yields maximum changes in the p H associated with

the subsequent dimerization. Both rate an d equilibrium constants

for the dimerization process can

be

obtained fro m analysis of the

p H decay curves.

Experimental Section

[F?(dien)Ip. This compound, used to prepare the corresponding aquo

species, was prepared from PtI,.H,O, which in tur n was prepared from

K,PtCl, by treatm ent with KI as reported by Watt and Cude?

[Pt(dien)(OH ,)](NO,),. A stock solution of the aquo complex in water

was prepared by heating

2

mmol of the iod ide complex with

4

mmol of

AgN 03 n about

25

mL of water at

50

for 3 h. The reaction mixture

was then centrifuged to remove the AgI precipitate, and the solid was

washed three times with small portions of water. The washings were

added to the decan tate. This solution was then rotary evaporated to

dryness and carefully diluted to

10.0

mL in a volumetric flask.

Titration and pH Recording Procedures. Titrations and kinetic runs

were carried out in a thermostated IO-mL cell, which was fitted with

appropriate electrodes and a bu ret. Titrations and kinetic runs were

carried out under an atmosphere of nitrogen. The pH was determined

with a Corning Model 10pH meter with an expanded scale. The output

of the meter was connected to a Houston Instruments Omniscribe strip

chart recorder. The temporal stability of the system was tested to insure

essentially zero drift over several hours before any kinetic runs were

made.

In

he kinetic runs, the pH was monitored for at least 12 h, with

the recorder set up to give

full

scale deflection with

a

change of

1 OO

pH

unit.

Results

pK,

Determination.

Th e concentration of stock solution and

the pK, of Pt(dien)(OH2)2+were both determined by titrations

of 1 OO-mL portions of the stock solution (ab out 0.2

M )

diluted

with 2.00 mL of water with 0.1000

N

N aO H in a thermostated

titration cell. The titration was carried ou t rapidly to m inimize

complications from dimerization. Th e pK, (5.87 .02) was taken

as the p H at half neutra l izat ion.

Analysis

o the

Rate Data.

The basis

of

the rate determinations

is the shift in the titration curve of Pt(dien)(O H2)+, which results

from the dimerization process as formulated in eq

3.

W e have

written computer procedures using RS /l software resident in a

VAX-8 600 computer to gen erate simulated titration curves based

on th e full equilibrium model, including the dimerization process.

After determinin g the pK, in a separa te titration , we ran simu lated

titration curves to estimate the p H changes to be expected from

the slow dimerization following rapid partial neutralization. This

chang e is shown in Figure

1

as the difference in p H a t

a

given

extent of neutralization betw een the curve for Kd

= 0

and the curve

for a given

K d

value. Th e dimer curve in Figure 1 corresponds

approximately to the experimen tal conditions employed in kinetic

runs and to Kd

=

108

M- ,

the value determined subsequently

on

the basis of the equilibrium composition of the solutions employed

in the kinetic

runs. On

he basis of Figure 1, we estimated that

the p H would change by more than half a p H unit after 10-20%

(9)

Watt,

G.

W.; Cude, W.

A. Inorg. Chem. 1968, 7, 335.

10)

Alcock, R. M.; Hartley,

F.

R.; Rogers,

D.

E. J Chem.

SOC.,

alton

1973, 1070.

0 2

0 4 0 6

O B

1 0

m l

NaOH

Figure

1.

Effect of dimerization on the titration curve of

0.05 M

mo-

noaquo platinum complex titrated with 0.100

M

NaOH for pK, =

5.87

and Kd

= 108.

' T

I

t , hr

Figure

2.

Decay curve reflecting the dimerization reaction of Pt-

(dien)(OH2)2+with Pt(dien)(OH)+ at

35

OC: A,, =

0.0399 M; Bo

=

0.00609 M.

titration for Kd values near 1 00 and

0.05 M

initial concentration

of complex.

The experimentally determined p H decay curve for one of the

kinetic

runs

is

shown

in

Figure 2. Over the 12 h of the experiment,

the pH changes by about

0.6

unit, in accord with the expectations

of the equilib rium model show n in Figure 1 with a Kd value of

about 108 and 12% neutralization.

The pH vs. time curves for partially neutralized solutions,

diluted to about 0.05

M

in Pt, were then used to determine the

concentrations of Pt-OH ?+ =

A ,

P t - O H +

=

B, and dimer =

D

as a function of time as follows: For each p H value, the ratio

B / A

was calculated from

p H

=

pK, log B / A )

(4)

Since Bo and Ao, he initial con centrations of base and acid forms

before any dim er formed, were known from the stoichiometry,

the concentrations of dimer and of base and acid forms a t any

time were then calculated from

(5)

/ A =

Bo D ) / A o D )

The concentration of Pt(dien)(OH )+

= Bo D ) ,

calculated from

(4)

and (5) , is shown as a function of time for one of the kinetic

runs

in Figure

3.

Figure

3

also includes the curve calculated by

a least-squares linear regression fit of the d ata, assum ing first-order

kinetics, i.e.

6 )

= B , B o

where B , is the equilibrium concentration of Pt(d ien)(O H)+ and

k

is the first-order rate constant for the approach to equilibrium.

The experimentally determined first-order rat e constant,

k,

an

be used t o calculate the ra te constants

kd

and

k4 on

he bas is of

an a ssumed rate law. If we assume second-order dimerization

and a first-order reverse reaction, the rate law can be form ulated

rate

=

d B / d t

= kdAB k4D

(7)



Mon oaquo Com plexes o f P t ( I1 )

Inorganic Chemistry, Vol.

26 No . 7,

1987

999

0.0067

0

0 0 4

PtOH)

002

I

2 4 E

10

12

0 . o o o i

t , hr

Figure

3.

Decay curve of P t(dien )(OH )+ calculated from the

pK, of

P t ( d i e ~ ~ ) ( o H ~ ) ~ +

5.87

and the data in Figure

2.

The

corresponding

least-squares regression equation is [Pt(dien)(OH)+]

= 0.00 1 19

0.00490 exp(-1.18

X

lo4

1 .

Table I.

Rate

and

Equilibrium Data for the Dimerization of

Pt(dien)(OH2)2+ t

35 OC

run

no.

A

Bo

D , Bo B,)

Kd/M-

1

0.0399 0.006 09 0.004 90

118

2

0.0406 0.005 64 0.004 39 91

mean

108 10

~

run

no.

104k/s- 104kd/M-

S-'

1O4kd/M-

1

1.18 .04 33.4 0.28

2 1.19 0.02 32.5 0.33

mean 33 1

0.30 0.03

Und er the conditions employed, only a small fraction of the acid

form will react,

so

that the reaction can be treated as a pseudo-

first-order reversible reaction with

dd t

=

kdA.

The observed

first-order rate constant,

k ,

can be identified with

kdt k4.

Furthermore,

kd

=

k d , / A ,

and

Kd = kd1k-d

=

D,/A,B, , so

all

three constants can be calculated from the data. Results for two

separate kinet ic runs a t

35 O C

ar e collected in Tab le

I.

Discussion

T h e di me ri za ti on co ns ta nt f or P t ( d i e ~ ~ ) ( o H ~ ) ~ + ,

08 10M-I,

reported here is close to the

132

M-' reported for the corresponding

Pd complex at

25

0C.3*s

or a

0.10

M

solution at p H

=

pKa, more

than half of the complex is in the form of t he dimer. Of course,

as the p H moves away from the pKa and for more dilute solutions

the extent of dimerization rapidly becomes negligible. Th e effect

of pH and of total concentration of platinum on th e fractional

populations of the dimer is shown in Figure

4.

The fractional

populations were calculated from th e equilibrium model, which

takes into account both dimerization an d the ac idlba se equilib-

rium. For solutions more dilute than abo ut

0.003

M in Pt, the

fractional population of dimer never exceeds IO , even a t pH =

pKa where its concentration is a maxim um.

It is not surpris ing that the dimerizat ion of P t(die n)(H 20) 2+

has not been noticed in connection with an y of the kinetic studies

that have been done on the compound. Much of that work in-

volved spectrophotometric analysis tha t required relatively dilute

solutions. In addition, much of th at work was done at relatively

low pH , where the aq uo species prevails, or at high pH , where

o E T

F

r

- p t

0 0030

--3-

C P t - 0.0100

0

p t 0 0300

o S P t -

O.lOO0

n

0 2

0 0

3 0

4 0

5 0

6 7 0 8 0

9 0

0 2

0 0

3 0

4 0

5 0 6 0

7 0 8 0

9 0

PH

Figure

4.

Effect of pH and total platinum concentration

on

he fractional

population of dimers.

the hydroxo form prevails. Th e comparative sluggishness of the

dimerization reaction relative to com peting reactions probably

also contributed to its neglect. Though the population distribution

shown in Figure

3

and the sluggishness of the dimerization reduce

the chances that the process will have an y significant effect on

reactions of the aquo complex, there may be conditions where

dimerization is an importan t complication. Th e addition of basic

ligands whose conjugate acids have pKa values comparable to th e

pKa of the dien species, abou t

6,

will yield solutions buffered n ear

the pKa, where the equilibrium frac tion of dimer is a max imum .

If concentrated solutions of such mixtures are allowed to equil-

ibrate, the concentration of dimer may be significant.

The close similarities in the pKa and

Kd

for the parallel platinum

and palladium dimers add support to Martin's efforts to employ

palladium analogues to model the detailed solution chemistry of

the more sluggish pla t inum c ~m pl ex es . ~he palladium complex

is somewhat less acidic (pKa

=

7.74

in

0.5

M

KN03

t

21

O C

vs.

5.87

a t 35

O C

or

6.13

a t

25

OC l0 for the platinum analogue).

However, the dimerization constants are both close to

100,

so

the

significance of th e dimer species in the two cases is compa rable.

The p H relaxation approach , guided by compute r modeling as

employed in this study, is currently being applied to th e somewhat

faster dimerization processes of mixed amin o acid-Me2SO-aquo

complexes of platinum. Th e same appr oach could very likely

be used to determine the much fas ter dimerization rate of the

parallel Pd(dien) (OH 2)2+ pecies. The success is fitting the ti-

tration data for the palladium complex to an equilibrium model

suggests that t he ra te of dimerization for the palladium species

is at least

100-1000

times faster than that of the platinum species,

for which an ordinary titration curve shows

no

perceptible deviation

from ideal behavior.

Acknowledgment

is made to the .donors of the P etroleum R e-

search Fund , administered by the American C hemical Society,

for support of this research.

Registry

No.

Pt(dien)(OH2),

48102-16-5;

Pt(dien)(OH)*,

48102-

15-4.

(1

1)

Erickson,

L. E.;

Burgeson,

I.

E.;

Eidsmoe,

E.;

Larsen,

R.

G.,

manuscript

in preparation.

equilibrium and kinetic studies of monoaquo complexes of platinum(i1). 2. dimerization of pt (dien)...

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